Evaluation of neoadjuvant immunotherapy plus chemotherapy in Chinese surgically resectable gastric cancer: a pilot study by meta-analysis.

Background: Recently, the use of immunochemotherapy in the treatment of advanced gastric cancer (GC) has been increasing and programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy has become the first-line treatment for advanced GC. However, few studies with small sample sizes have examined this treatment regimen to assess its effectiveness and safety in the neoadjuvant treatment phase of resectable local advanced GC. Materials and methods: Herein, we systematically searched PubMed, Cochrane CENTRAL, and Web of Science for clinical trials on neoadjuvant immunochemotherapy (nICT) in advanced GC. The primary outcomes were effectiveness [evaluated by major pathological response (MPR) and pathological complete response (pCR)] and safety [assessed by grade 3-4 treatment-related adverse events (TRAEs) and postoperative complications]. A meta-analysis of non-comparative binary results was performed to aggregate the primary outcomes. Direct comparative analysis was used to compare pooled results of neoadjuvant chemotherapy (nCT) with nICT. The outcomes emerged as risk ratios (RR). Results: Five articles with 206 patients were included, and all of them were from the Chinese population. The pooled pCR and MPR rates were 26.5% (95% CI: 21.3%-33.3%) and 49.0% (95% CI: 42.3%-55.9%), while grade 3-4 TRAEs and post-operative complication rates were 20.0% (95% CI: 9.1%-39.8%) and 30.1% (95% CI: 23.1%-37.9%), respectively. Direct comparison showed that with the exception of grade 3-4 TRAEs and postoperative complications, all outcomes including pCR, MPR, and R0 resection rate favoured nICT to nCT. Conclusion: nICT is a promising strategy for use as an advisable neoadjuvant treatment for patients with advanced GC in Chinese population. However, more phase III randomized controlled trials (RCTs) will be required to further consolidate the efficacy and safety of this regimen.

Endoluminal Vacuum-Assisted Closure Therapy for Upper Gastrointestinal Leak, Perforation, and Fistula: A Case Series and Literature Review.

BACKGROUND: With the increasing incidence of upper digestive tract tumors, more upper digestive tract surgeries are performed each year, and surgeons have difficulty in the postoperative management of gastrointestinal anastomotic fistula. The use of a new minimally invasive technique, endoluminal vacuum-assisted closure (E-VAC), has increased the success rate of the treatment of gastrointestinal fistula. METHODS: We present 6 cases of gastrointestinal fistula treated in our hospital in 2021: 3 cases of anastomotic fistula after esophageal cancer surgery, 2 cases of anastomotic fistula after gastric cancer surgery, and one case of esophageal rupture after trauma. With E-VAC and other adjuvant treatment measures, the gastrointestinal fistulas were eventually closed or significantly reduced. RESULTS: Both local and systemic infections in all 6 patients were controlled with the use of E-VAC device, resulting in significant reduction or closure of fistulas. CONCLUSION: E-VAC devices can effectively help in the removal of the exudate and necrotic tissue around the fistula, promote the proliferation of granulation tissue, and support closure of the fistula. However, further improvements to the device are needed to improve patient comfort and operational safety.

Can the carbon metabolic activity of biofilm be regulated by the hydrodynamic conditions in urban rivers?

Hydrodynamic regulation is widely used to improve the water quality of urban rivers. However, it is yet to explore substantially whether hydrodynamics could regulate the metabolic activity of biofilm in such aquatic systems. Herein, the pilot experiment of hydrodynamics in the rotation tanks was designed, including two experiment phases, namely constant flow and adjusting flow for 21 days and 14 days, respectively. In constant flow phase, biofilms grew in five shear stress gradients (R1-R5, 0.0044- 0.12 Pa). The carbon metabolic rate (k) of mature biofilms evaluated by BIOLOG ECO microplates showed a hump-shaped relationship with increasing shear stress, with R3 (0.049 Pa) the highest, while R5 (0.12 Pa) the lowest. To verify whether the metabolic activity of biofilm cultured at constant flow phase can be regulated by shear stress, we initiated the adjusting flow phase, and shear stress in reactors was reset uniformly at 0.049 Pa (with the highest k). Results showed the carbon metabolic activity of biofilm in reactor R4 and R5 increased rapidly by day 3, and there was no significant difference between the carbon metabolic rates among the five treatments by day 14. Meanwhile, the utilization levels of polymers and carbohydrates by biofilms were significantly different among the five treatments after hydrodynamic regulations. These results suggested that the total carbon metabolic activity of biofilm can be regulated by hydrodynamics, while the divergent changes of the specific carbon source category might affect the biofilm-mediated carbon biogeochemical processes, which should be considered for the application of hydrodynamic regulation in river ecological restoration projects.

LncRNA FEZF1-AS1 Promotes Multi-Drug Resistance of Gastric Cancer Cells via Upregulating ATG5.

Long non-coding RNAs (lncRNAs) play important roles in human cancers including gastric cancer (GC). Dysregulation of lncRNAs is involved in a variety of pathological activities associated with gastric cancer progression and chemo-resistance. However, the role and molecular mechanisms of FEZF1-AS1 in chemoresistance of GC remain unknown. In this study, we aimed to determine the role of FEZF1-AS1 in chemoresistance of GC. The level of FEZF1-AS1 in GC tissues and GC cell lines was assessed by qRT-PCR. Our results showed that the expression of FEZF1-AS1 was higher in gastric cancer tissues than in adjacent normal tissues. Multivariate analysis identified that high level of FEZF1-AS1 is an independent predictor for poor overall survival. Increased FEZF1-AS1 expression promoted gastric cancer cell proliferation in vitro. Additionally, FEZF1-AS1 was upregulated in chemo-resistant GC tissues. The regulatory effect of FEZF1-AS1 on multi-drug resistance (MDR) in GC cells and the underlying mechanism was investigated. It was found that increased FEZF1-AS1 expression promoted chemo-resistance of GC cells. Molecular interactions were determined by RNA immunoprecipitation (RIP) and the results showed that FEZF1-AS1 regulated chemo-resistance of GC cells through modulating autophagy by directly targeting ATG5. The proliferation and autophagy of GC cells promoted by overexpression of LncFEZF1-AS1 was suppressed when ATG5 was knocked down. Moreover, knockdown of FEZF1-AS1 inhibited tumor growth and increased 5-FU sensitivity in GC cells in vivo. Taken together, this study revealed that the FEZF1-AS1/ATG5 axis regulates MDR of GC cells via modulating autophagy.

Environmental contaminant BPA causes intestinal damage by disrupting cellular repair and injury homeostasis in vivo and in vitro.

Our previous studies have shown that the environmental contaminant bisphenol A (BPA) exhibits strong intestinal toxicity and can readily cause intestinal barrier dysfunction. However, the causal relationship between adverse biological processes of BPA-induced intestinal tissue and the role of key signaling molecules in it requires further investigation. In this study, we established a mouse and intestinal epithelial cell model of BPA treatment to determine the underlying molecular mechanisms of BPA-induced intestinal injury. The results showed that the BPA treatment increased the intestinal permeability and disrupted the barrier function by increasing the chemical marker content and tight junction expression in intestinal tissues and blood circulation. BPA also altered the oxidative and antioxidant status of intestinal epithelial cells by increasing ROS and RNS contents and decreasing the activity levels of SOD, GPx, CAT, and T-AOC. BPA further induced inflammatory responses by upregulating the gene abundance of key factors of the innate immune system (TLR2, TLR4, MyD88, and NF-κB), the transcriptional activity of NF-kB, and the secretion of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α). Moreover, apoptosis was activated by BPA, whereas cell proliferation was inhibited by BPA. Mechanistically, co-treatment of intestinal epithelial cells with BPA using the oxidative stress scavenger NAC, the NF-κB-specific inhibitor JSH-23, and the apoptosis inhibitor Z-VAD-FMK, respectively, showed that BPA activates the innate immune response by inducing oxidative stress. Consequently, apoptosis is promoted, and cell proliferation is inhibited, ultimately disrupting the intestinal barrier function. Our findings provide insight into the pathogenesis of BPA-induced gut injury.

Antibiotic Alleviates Radiation-Induced Intestinal Injury by Remodeling Microbiota, Reducing Inflammation, and Inhibiting Fibrosis.

Radiation-induced intestinal injury is a common complication of abdominal radiation therapy. However, the pathological features of radiation-induced intestinal injury and its therapeutic regimen are not very clear. The aim of this study was to investigate the effects of antibiotic pretreatment on radiation-induced intestinal injury. Abdominal radiation disrupted the intestinal microbiota balance and significantly reduced bacterial diversity in mice. Antibiotic cocktail (Abx) pretreatment effectively removed the intestinal microbiota of mice, and metronidazole also reduced the diversity of intestinal bacteria to some extent. Two antibiotic pretreatment regimens improved the reconstitution ability of the gut microbiota in mice after radiation. Further experiments showed that Abx pretreatment effectively reduced the content of lipopolysaccharide (LPS) and inhibited the TLR4/MyD88/NF-κB signaling pathway in the ileum. In addition, Abx pretreatment regulated macrophage cell polarization in the ileum, downregulated TGF-ß1, phosphorylated Smad-3 and α-SMA protein levels, and upregulated E-cadherin protein expression. Eventually, Abx pretreatment significantly improved the survival rate and attenuated intestinal injury of mice after radiation by reducing inflammation and preventing intestinal fibrosis. These results revealed that antibiotic pretreatment can effectively alleviate gut microbiota turbulence and intestinal damage caused by abdominal radiation in mice. Collectively, these findings add to our understanding of the pathogenesis of radiation enteritis.

Long non-coding RNA MALAT1 activates autophagy and promotes cell proliferation by downregulating microRNA-204 expression in gastric cancer.

Gastric cancer (GC) is one of the major diseases that threaten human health. Although the development of novel drugs has significantly improved the efficacy of GC chemotherapy, the 5-year survival rate of patients with GC remains unsatisfactory. In the present study, the role and mechanism of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in GC proliferation was investigated. Clinical specimens and cancer cells were analyzed by western blotting or immunofluorescence. Reverse transcription-quantitative polymerase chain reaction analysis of 57 paired GC and non-tumorous tissues revealed elevated expression of MALAT1 in GC tissues compared with controls. In addition, increased MALAT1 was associated with elevated levels of microtubule-associated protein 1 light chain 3ß (LC3B) and antigen Ki67, which are autophagy and proliferation markers, respectively. MTT and colony formation assay results demonstrated that MALAT1 promoted GC cell proliferation. To the best of our knowledge, the present study was the first to demonstrate that upregulated MALAT1 was associated with increased autophagy activation in GC tissues. Furthermore, this study reported that MALAT1 increased cell proliferation and enhanced autophagy activation in GC cells. In addition, the results revealed that MALAT1 inhibited microRNA (miR)-204 expression in GC cells. The present study also demonstrated that miR-204 repressed autophagy through the downregulation of LC3B and transient receptor potential melastatin 3 expression in GC cells. These results indicated that MALAT1 activated autophagy and promoted cell proliferation by downregulating miR-204 expression in GC.

Effect of early oral feeding on gastrointestinal function recovery in postoperative gastric cancer patients: a prospective study.

PURPOSE: To prospectively compare the early and late postoperative oral feeding of operated gastric cancer patients on the gastrointestinal function recovery. METHODS: 198 gastric cancer patients treated in our hospital from June 2015 to June 2017 were enrolled. Patients were randomized into two groups, early feeding group and late feeding group. All patients underwent the same surgical procedure, which was laparoscopic radical gastrectomy. Time of the first postoperative exhaust and defecation was recorded. Fasting venous blood samples were collected on the day of surgery and 1, 3, and 5 days after surgery. Serum levels of gastrin and motilin were assessed. RESULTS: Time of the first postoperative exhaust and defecation in the early feeding group was 2.05±0.71 days and 3.58±0.92 days, respectively. In the late feeding group they were 2.50±0.91 days and 5.17±1.0 days, respectively (p=0.008, p=0.002). Serum levels of gastrin and motilin in the early feeding group were remarkably higher than those of the late feeding group on the 3rd and 5th postoperative day. Univariate analysis showed that time of the first postoperative feeding, operation time and postoperative gastrin level on the 3rd day were factors remarkably affecting the time of the first postoperative exhaust (p=0.003, p=0.043, p=0.032, respectively). Multivariate analysis revealed that the time of postoperative feeding was an independent factor affecting the time of the first postoperative exhaust (Odds ratio/OR=0.986, 95%CI=0.974-0.997, p=0.027). CONCLUSIONS: Early oral feeding promotes the recovery of postoperative gastrointestinal function in gastric cancer patients, and doesn't increase the incidence of related complications and adverse events.

Techniques and pitfalls of laparoscopic paraesophageal hernia repair in severe kyphoscoliosis patients.

BACKGROUND: Increasing evidence suggests that kyphoscoliosis may play a role in the pathophysiology of paraesophageal hernia development. The presence of severe kyphoscoliosis not only increases the incidence of paraesophageal hernia but also increases the risk of hiatal hernia (HH) repair. Moreover, the technical skills and the pitfalls of laparoscopic repair of HH in this special condition have yet been described. METHODS: The technical skills, experience and pitfalls of laparoscopic paraesophageal hernia repair in severe kyphoscoliosis patients were described. These include perioperative care of patients' pulmonary function, patients' operating position and trocar placement, and the key steps and risks of laparoscopic HH repair in this special condition. RESULTS: Paraesophageal HHs were successfully laparoscopically repaired, and prolonged hospital stay was due to post-operative pulmonary complications. CONCLUSION: These techniques are essential to minimise the perioperative complications in laparoscopic paraesophageal hernia repair in severe kyphoscoliosis patients, and great pulmonary care is required in these patients.

Relationship between gastric cancer tau protein expression and paclitaxel sensitivity.

The abnormal expression of Tau protein in breast cancer tissue affects paclitaxel sensitivity. The abnormal expression also exists in gastric carcinoma. Therefore, we speculate that the expression levels of Tau protein is closely related to paclitaxel sensitivity in gastric cancer, thus affecting the efficacy of paclitaxel. In this study, we used immunohistochemical methods to detect Tau protein expression levels in 47 cases of gastric cancer specimens. We also used Western blot to detect the level of Tau protein expression in gastric cancer cell lines and to check the efficacy of paclitaxel in vitro application. Findings indicate that Tau protein expression rate can reach as high as (+ +-+ + +) 63.83 % in gastric cancer. Paclitaxel induces inhibition and apoptosis with low expression of Tau protein in gastric cancer cell lines (P < 0.05). The level of Tau protein expression is significantly correlated with paclitaxel efficacy. If confirmed by further studies, the Tau protein can be another useful marker of gastric cancer, thereby leading to the application of paclitaxel in cancer treatment.